Effects of resveratrol in experimental and clinical non-alcoholic fatty liver disease

Table 1 Rodent resveratrol studies with histological liver data

Ref.	Focus	Model	RSV dose	RSV exposure(wk)	Histology/LW	TG/CH content	LiverAMPK activation	Suggested RSV actions/mechanisms
Baur et al[37] (2006)	Longevity	Middle-aged DIO mice	22.4 mg/kg BW = 0.04% in diet	27	+/+	ND	+	Elevated PGC-1α deacetylation as marker of enzymatic SIRT1 activity. Phosphorylation of ACC
Ahn et al[65] (2008)	NAFLD/NASH	DIO mice (1% CH in diet)	1.25 g/kg diet	8	+/+ Decrease in NASH	+/-	ND	Reduced hepatic expression of FAS, PPARγ, CD36. Increased PPARα expression
Kang et al[46] (2010)	Insulin signaling	DIO mice	30 mg/kg BW	2	+/ND	ND	-	Increased Akt phosphorylation, improving insulin signaling
Labbé et al[109] (2011)	NAFLD, metabolic profile, longevity	Werner syndrome mice	0.04% RSV in diet	Life-long ( ≤ 22.5 mo)	+/ND	ND	-	Decreased FAS expression Decreased HCC prevalence
Tauriainen et al[115] (2011)	Obesity, NAFLD	DIO mice	2 or 4 g/kg diet	15	+/ND	ND	ND	Increased SIRT1 expression in liver tissue. High-dose most effective
Cho et al[111] (2012)	NAFLD	DIO mice (1% CH in diet)	7 mg/kg BW or 30 mg/kg BW	10	+/ND	+/+	ND	Suppressed FAS activity. Activation of FA β-oxidation in liver. The lower dose is more efficient than the higher dose
Zhou et al[108] (2012)	Overall transcriptomic and metabolic profiling	DIO mice	0.04% or 0.02% RSV + quercetin 0.02%	26	+/ND	-/+	ND	Modulation of inflammation and FA β-oxidation. Combination with quercetin was more effective than RSV alone
Jeon et al[51] (2012)	Cognitive deficit	DIO mice	200 mg/kg BW	20	+/ND	ND	ND	Attenuation of hepatic lipid peroxidation and macrophage infiltration
Shiozaki et al[97] (2012)	Longevity	SAMP10 mice	0.04% RSV	20	+/ND	ND	ND	Inhibition of ACC. Improved mitochon-drial number, redox status and activity
Gao et al[114] (2013)	NAFLD	T0901317-treated mice	200 mg/kg BW	< 1	+/+	+/ND	+	Inhibition of ACC. Unchanged expression SREBP-1c and related genes
Li et al[110] (2013)	NAFLD	HFS mice	50 mg/kg BW	3	+/ND Decrease in NASH	ND	ND	Inhibition of NF-κB-induced inflamma-tion and MDA-induced oxidative stress. Protection against NASH fibrosis
Bujanda et al[49] (2008)	NAFLD	Fasting/feeding special diet, rats	10 mg daily	4	+/-	ND	ND	Hepatic TNF-α decrease. Improved oxidant/antioxidant markers (MDA, NOS, SOD, e.g., catalase)
Shang et al[74] (2008)	NAFLD	HFD rats	100 mg/kg BW	10	+/+	+/-	+	Suppressed SREBP-1c and FAS gene expression
Poulsen et al[76] (2012)	NAFLD	HFD rats	100 mg daily	8	+/-	+/ND	-	Increased UCP2 expression Increased mitochondrial number
Gomez-Zorita et al[103] (2012)	NAFLD	Obese Zucker rats	15 mg/kg BW or 45 mg/kg BW	6	+/+	+/?	ND	Increased CPT-1α and ACO No effect on activity of lipogenic enzymes
Bagul et al[94] (2012)	Oxidative stress	High fructose fed rats	10 mg/kg BW	8	+/ND	ND	ND	Attenuation of hepatic oxidative stress, e.g., with increased level of NRF2
Franco et al[96] (2013)	Oxidative stress and NAFLD	Obese ‘early weaned’ rats	30 mg/kg BW	4	+/ND	+/ND	ND	Decreased markers of oxidative stress
Xin et al[66] (2013)	NAFLD	HFS rats	50 or 100 mg/kg BW	13	+/ND	+/+	ND	Decreased hepatic LDLr and SRB1 mRNA and protein express
Cho et al[67] (2008)	Hyperlipidemia	HFD hamsters	0.25 g/kg diet	8	+/+	+/+	ND	Decreased HMG-CoA expression and modulated lipoprotein expression
Burgess et al[110] (2011)	Metabolic syndrome	HFD mini-swine	100 mg/kg daily	11	(+)/ND	ND	ND	Improved insulin sensitivity

+ positive finding; - negative finding; ND: Not determined. LW: Liver weight; BW: Body weight; TG: Triglyceride; CH: Cholesterol; AMPK: AMP-activated protein kinase; PGC-1α: Peroxisome proliferator-activated receptor gamma coactivator 1 α; SIRT1: Silent information regulation 2 homolog 1; ACC: Acetyl-CoA carboxylase; NAFLD/NASH: Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis; DIO: Diet induced obesity; FAS: Fatty acid synthase; PPARγ/α: Peroxisome proliferator-activated receptor γ/α; SAMP10: Senescence-accelerated mouse P10; HCC: Hepatocellular carcinoma; FA: Fatty acids; SREBP-1c: Sterol regulatory element-binding protein-1c; TNF-α: Tumor necrosis factor-α; MDA: Malondialdehyde; NOS: Nitric oxide synthase; SOD: Superoxide dismutase; HFD: High fat diet; UCP2: Uncoupling protein 2; CPT-1α: Carnitine palmitoyl transferase-1α; ACO: Acyl-coenzyme A oxidase; NRF2: Nuclear factor-like 2; HFS: High fat/sucrose diet; LDLr: Low-density lipoprotein receptor; SRB1: Scavenger receptor class B member 1; HMG-CoA: 3-hydroxy-3-methylglutaryl-coenzyme A.